A. Guida

Abnormally high prevalence of major components of the metabolic syndrome in subjects with early-onset idiopathic venous thromboembolism

BACKGROUND Although patients with idiopathic VTE are at higher than normal risk of asymptomatic atherosclerosis and of cardiovascular events, the impact of cardiovascular risk factors on VTE is poorly understood. OBJECTIVE To assess the prevalence of the metabolic syndrome and of its components in patients with early-onset idiopathic VTE. METHODS As many as 323 patients referred to our Thrombosis Ward for a recent (<6-months) early-onset idiopathic venous thromboembolism (VTE), were compared with 868 gender- and age-matched subjects, in whom a history of venous thrombosis had been excluded, referred during the same period time to our Ward. All had undergone a clinical assessment for smoking habits and for the presence of the components of the metabolic syndrome. RESULTS The metabolic syndrome was detected in 76/323 cases (23.5%) and in 81/868 controls (9.3%) (p<0.001; OR:2.990; 95%C.I.:2.119-4.217). Smoking was more common in patients with idiopathic VTE than in controls. In addition to the metabolic syndrome as a whole, its major individual determinants (arterial hypertension, impaired fasting glucose plasma levels, abdominal obesity, hypertriglyceridemia, low HDL-cholesterol) significantly correlated with idiopathic VTE (p always <0.05). The prevalence of thrombotic events was lower in females than in males (p=0.000; OR:2.217), the latter being most often hypertensives, smokers, hypertriglyceridemics, carriers of a metabolic syndrome and of impaired fasting glucose than females. In a multivariate analysis, arterial hypertension, impaired fasting glucose, abdominal obesity, and hypercholesterolemia independently predicted idiopathic venous events. CONCLUSIONS Both metabolic syndrome as a whole and its major components individually considered, independently predict early-onset idiopathic VTE.

Air pollution, vascular disease and thrombosis: linking clinical data and pathogenic mechanisms

Summary.  The public health burden of air pollution has been increasingly recognized over the last decades. Following the first assessed adverse effects on respiratory diseases and lung cancer, a large body of epidemiologic and clinical studies definitely documented an even stronger association of air pollution exposure with cardiovascular mortality and morbidity, particularly related to atherothrombotic (coronary and cerebrovascular) disease. Particulate matter (PM), mainly that with lower aerodynamic diameter (fine and ultrafine PM), is responsible for the most severe effects, due to its capacity to transport toxic substances deep into the lower airways. These effects have been shown to occur not only after short‐term exposure to elevated concentrations of pollutants, but even after long‐term relatively low levels of exposure. Vulnerable subjects (elderly persons and those with preexisting cardiopulmonary diseases) show the highest impact. Fewer and conflicting data also suggest an association with venous thromboembolism. Although not completely elucidated, a series of mechanisms have been hypothesized and tested in experimental settings. These phenomena, including vasomotor and cardiac autonomic dysfunction, hemostatic unbalance, oxidative stress and inflammatory response, have been shown to change over time and differently contribute to the short‐term and long‐term adverse effects of pollution exposure. Beyond environmental health policies, crucial for improving air quality and reducing the impact of such an elusive threat to public health, the recognition and assessment of the individual risk, together with specific advice, should be routinely implemented in the strategies of primary and secondary cardiovascular prevention.

Overcoming limitations of current antiplatelet drugs: A concerted effort for more profitable strategies of intervention

Abstract Platelets play a central role in the pathophysiology of atherothrombosis, an inappropriate platelet activation leading to acute ischemic complications (acute myocardial infarction, ischemic stroke). In view of this, platelets are a major target for pharmacotherapy. Presently, the main classes of antiplatelet agents approved for the use in such complications are aspirin and thienopyridines. Although antiplatelet treatment with these two types of drugs, alone or in combination, leads to a significant reduction of non-fatal myocardial infarction (−32%), non-fatal stroke (−25%), and of cardiovascular death (−17%), a residual risk persists. Newer antiplatelet agents have addressed some, but not all, these limitations. Vis-à-vis their net clinical benefit, the higher potency of some of them is associated with a rise in bleeding complications. Moreover, newer thienopyridines do not show advantages over and above the older ones as to reduction of stroke. A concerted effort that takes into consideration clinical, genetic, and laboratory information is increasingly recognized as a major direction to be pursued in the area. The well-established road signs of clinical epidemiology will provide major information to define newer potentially useful targets for platelet pharmacology.

Prevention of Venous Thromboembolism in Medical Patients with Thrombocytopenia or with Platelet Dysfunction: A Review of the Literature

Current guidelines for venous thromboembolism (VTE) primary prophylaxis are based on randomized clinical trials that exclude subjects at a potentially high bleeding risk. Thus no specific recommendation/algorithm for pharmacological prophylaxis in patients with thrombocytopenia and/or platelet dysfunction is available. Because at least 25% of subjects admitted to medical departments exhibit these conditions, information on this subject is provided here to optimize their VTE prophylaxis. Low platelet number/function and clotting abnormalities are common in patients with liver cirrhosis. However, these patients have a high incidence of portal and idiopathic venous thromboses, implying that cirrhotic coagulopathy does not protect against thrombosis. At variance with severe thrombocytopenia (< 50,000/μL), mild/moderate thrombocytopenia (> 50,000/μL) should not interfere with VTE prevention decisions. In severe thrombocytopenia, prophylaxis should be considered on an individual basis, however. In patients with antiphospholipid antibodies and thrombocytopenia, a thrombotic tendency is usually associated rather than a bleeding risk. VTE prophylaxis in high-risk conditions is thus suggested in these patients. Except in cases with contraindications to anticoagulation, antithrombotic prophylaxis should be always considered in hospitalized cancer patients with thrombocytopenia, especially in those with hematologic malignancies and multiple VTE risk factors. Aspirin treatment is not as effective as heparins in lowering the risk of VTE. Studies in stroke suggest that thromboprophylaxis with heparins is safe in patients with ischemic stroke undergoing aspirin treatment. The need for VTE prophylaxis in patients on chronic treatment with aspirin and/or clopidogrel should be evaluated after assessing the individual risk-benefit ratio.

The thromboembolic risk in giant cell arteritis: A critical review of the literature

Giant cell arteritis is a systemic vasculitis characterized by granulomatous inflammation of the aorta and its main vessels. Cardiovascular risk, both for arterial and venous thromboembolism, is increased in these patients, but the role of thromboprophylaxis is still debated. It should be suspected in elderly patients suffering from sudden onset severe headaches, jaw claudication, and visual disease. Early diagnosis is necessary because prognosis depends on the timeliness of treatment: this kind of arteritis can be complicated by vision loss and cerebrovascular strokes. Corticosteroids remain the cornerstone of the pharmacological treatment of GCA. Aspirin seems to be effective in cardiovascular prevention, while the use of anticoagulant therapy is controversial. Association with other rheumatological disease, particularly with polymyalgia rheumatica is well known, while possible association with antiphospholipid syndrome is not established. Large future trials may provide information about the optimal therapy. Other approaches with new drugs, such as TNF-alpha blockades, Il-6 and IL-1 blockade agents, need to be tested in larger trials.

Acquired Haemophilia A in the Elderly: Case Reports

Acquired hemophilia A (AHA) is a very rare disease, caused by the development of autoantibodies, directed against circulating factor VIII of coagulation. Age distribution is bimodal, with a first peak occurring among young women in the postpartum period, and a second major peak of incidence among elderly patients in whom it is frequently associated with malignancy and drugs. This disease often represents a life-threatening bleeding condition, especially in the elderly, thus requiring a prompt therapeutic intervention, including control of acute bleeding and eradication of the inhibitor by immunosuppressive therapy. The diagnosis of AHA should be considered in any elderly patient who presents with bleeding and prolonged activated Partial Thromboplastin Time. Moreover, the coexistence of a series of underlying diseases associated with AHA should be always searched for. An early recognition and an adequate treatment of this coagulation disorder and of the possible associated diseases play a significant role for a favourable outcome, but concomitant morbidities in the elderly may limit aggressive therapy and may complicate the clinical scenario. We report 3 consecutive elderly patients successfully treated with recombinant activated factor VII and standard immunosuppressive regimens, with remission of the disease.

Rate and duration of hospitalization for deep vein thrombosis and pulmonary embolism in real-world clinical practice

Abstract Background Current guidelines recommend initial treatment with anticoagulants at home in patients with acute deep vein thrombosis (DVT) and in patients with low-risk pulmonary embolism (PE) with adequate home circumstances. However, most of the patients with acute venous thromboembolism (VTE) are currently hospitalized regardless of their risk of short-term complications. Aim of the study To assess the proportion of outpatients with acute VTE initially treated in hospitals, to assess the mean duration of hospitalization, and to identify predictors for in-hospital or home treatment. Methods Data of Italian patients enrolled in the RIETE registry from January 2006 to December 2013 were included. Results Altogether 766 PE and 1,452 isolated DVT were included. Among PE patients, mean PESI score was 84 points (SD 35), and 56% of patients had a low-risk PESI score (<85). In all, 53.7% of DVT and 17.0% of PE were entirely treated at home, and 38.2% of DVT patients and 19.9% of PE patients were hospitalized for ≤5 days. On multivariate analysis, low PESI score was not independently associated with the hospitalization of PE patients. Conclusions One in every two patients with DVT and five in every six with PE are still hospitalized. Key Messages A significant number of patients with venous thromboembolism (VTE) are still hospitalized for the acute phase of the treatment despite current guidelines recommending initial treatment with anticoagulants at home in patients with acute deep vein thrombosis (DVT) and in patients with low-risk pulmonary embolism (PE) with adequate home circumstances.

Acute coronary syndrome and severe haemophilia: An unusual association with challenging treatment

Acute coronary syndrome and severe haemophilia: An unusual association with challenging treatment -

Cardiovascular events in patients with antiphospholipid antibodies: strategies of prevention.

Antiphospholipid antibodies are a heterogeneous group of auto-antibodies against phospholipids-binding proteins. The antiphospholipid syndrome is an autoimmune disorder characterized by the clinical association of antiphospholipid antibodies with a condition of hypercoagulability that can affect any blood vessel. Involvement of larger vessels, such as arteries or veins, manifests in the form of thrombosis or thromboembolism, whereas involvement of small vessels manifests as thrombotic micro-angiopathy. The antiphospholipid syndrome is also characterized by the presence of recurrent fetal loss. Patients who are persistently positive for antiphospholipid tests, and who have an arterial thrombosis or venous thrombosis history, are at increased risk of recurrence. Oral anticoagulant therapy is the mainstay of treatment for the thrombotic manifestations of the syndrome. Therapy with anticoagulant drugs should be long-term. On the other hand, although the thromboembolic potential of antiphospholipid antibodies has been well documented, there is still no general consensus on the prophylactic treatment of antiphospholipid antibodies carriers who have never developed vascular/obstetric manifestations. The effect of primary prophylaxis in antiphospholipid antibodies positive individuals is not well known and no evidence-based recommendations exist for thrombosis prevention in these individuals. However, the presence of risk factors for thrombosis increases the risk of first event of antiphospholipid antibodies positive patients. In conclusion, there is still much to learn on primary prophylaxis of asymptomatic antiphospholipid antibodies carriers. Hopefully, evidence-based guidelines will be available in the future.

Molecular analysis and genotype-phenotype correlation in patients with antithrombin deficiency from Southern Italy

We sequenced the SERPINC1 gene in 26 patients (11 males) with antithrombin (AT) deficiency (22 type I, 4 type II), belonging to 18 unrelated families from Southern Italy. Heterozygous mutations were identified in 15/18 (83.3%) families. Of them, eight were novel mutations, each being identified in one family. Seven clearly cause impaired protein synthesis (four frameshift, one non-stop, one splicing and one 21bp deletion). One, present in a single patient, is a missense mutation thought to be causative because: a) it is absent in 100 chromosomes from controls; b) it involves a highly conserved amino acid, whose change is predicted to impair AT activity; c) no other mutation is present in the propositus. Severe mutations (i.e. nonsense, frameshift, deletions) were invariably identified in type I patients. In type II patients, 3/4 were missense mutations; the fourth leads to a 19 nucleotides shift in the stop codon. In addition to the type of mutation, the co-existence of other predisposing factors in most patients helps explain the severity of the present type I cases (age at first event, recurrence during prophylaxis). In the five families in which there was more than one member affected, the same genotype and a concordant clinical expression of the disease were found. We conclude that the molecular bases of AT deficiency in Southern Italy are different as compared to other geographic areas, and that molecular analysis and the study of the effect of the mutation may help predict the clinical expression of the disease.